Cationic mesoporous silica nanoparticles alleviate osteoarthritis by targeting multiple inflammatory mediators

Tongfei Shi; Jingtong Zhao; Kongrong Long; Mohan Gao; Fangman Chen; Xuenian Chen; Yue Zhang; Baoding Huang; Dan Shao; Chao Yang; Liang Wang; Ming Zhang; Kam W Leong; Li Chen; Kan He

doi:10.1016/j.biomaterials.2023.122366

Cationic mesoporous silica nanoparticles alleviate osteoarthritis by targeting multiple inflammatory mediators

Biomaterials. 2023 Dec:303:122366. doi: 10.1016/j.biomaterials.2023.122366. Epub 2023 Nov 4.

Authors

Tongfei Shi¹, Jingtong Zhao², Kongrong Long³, Mohan Gao², Fangman Chen⁴, Xuenian Chen⁵, Yue Zhang², Baoding Huang⁶, Dan Shao⁷, Chao Yang⁶, Liang Wang⁶, Ming Zhang², Kam W Leong⁸, Li Chen⁹, Kan He¹⁰

Affiliations

¹ Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China; School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, 510006, China.
² Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China.
³ Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China; Norman Bethune College of Medicine, Jilin University, Changchun, 130021, China.
⁴ National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, 510006, China.
⁵ School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
⁶ Department of Orthopedics, Academy of Orthopedics-Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510665, China.
⁷ School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, 510006, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China. Electronic address: shaodan@scut.edu.cn.
⁸ Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
⁹ Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China; School of Nursing, Jilin University, Changchun, 130021, China. Electronic address: chenl@jlu.edu.cn.
¹⁰ Department of Pharmacology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China. Electronic address: hek@jlu.edu.cn.

PMID: 37948854
DOI: 10.1016/j.biomaterials.2023.122366

Abstract

Osteoarthritis (OA) is a common and complex inflammatory disorder that is frequently compounded by cartilage degradation, synovial inflammation, and osteophyte formation. Damaged chondrocytes release multiple danger mediators that exacerbate synovial inflammation and accelerate the progression to OA. Conventional treatments targeting only a single mediator of OA have failed to achieve a strong therapeutic effect. Addressing the crucial role of multiple danger mediators in OA progression, we prepared polyethylenimine (PEI)-functionalized diselenide-bridged mesoporous silica nanoparticles (MSN-PEI) with cell-free DNA (cfDNA)-binding and anti-oxidative properties. In models of surgery-induced and collagenase-induced arthritis, we showed that these cationic nanoparticles attenuated cartilage degradation and provided strong chondroprotection against joint damage. Mechanistically, multiple target blockades alleviated oxidative stress and dampened cfDNA-induced inflammation by suppressing the M1 polarization of macrophages. This study suggests a beneficial direction for targeting multiple danger mediators in the treatment of intractable arthritis.

Keywords: Cell-free DNA; Inflammation; Mesoporous silica nanoparticles; Osteoarthritis; Reactive oxygen species.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell-Free Nucleic Acids* / metabolism
Cell-Free Nucleic Acids* / pharmacology
Cell-Free Nucleic Acids* / therapeutic use
Chondrocytes / metabolism
Humans
Inflammation / drug therapy
Inflammation / metabolism
Nanoparticles* / chemistry
Osteoarthritis* / drug therapy
Osteoarthritis* / metabolism
Silicon Dioxide / therapeutic use

Substances

Silicon Dioxide
Cell-Free Nucleic Acids